124 Letters and Correspondence

blood cell count increased from 0.4 X 10yL to 1.0 X 109/L in the first 10 days, only to exhibit an accelerated rise afterwards, the count reaching 36.5 X 109L on the 14th day. G-CSF was therefore discontinued (Fig. I ) . The peripheal smear revealed 2% blasts, 3% promyelocytes, 5% metamyelo- cytes, 14% bands, S8% polymorphonuclear leukocytes, 12% lymphocytes, and 6% normohlasts. Bone marrow aspirate exhibited hypercellularity and marked myeloid hyperplasia (myeloid/erythroid ratio, 8: I ) , with 1.0% blasts. The white blood cell count declined to 4.6 X 109/L in a period of 8 days. Daily peripheral blood smear examinations revealed the gradual resolution of leukoerythroblastosis. Subsequent bone marrow aspiration was unremarkable except for mild erythroid hyperplasia, with a blast count ofO.S%. On the confirmation of remission, the patient was discharged and was followed as an outpatient on a monthly basis. The patient is well and free of any evidence of relapse after 6 months of follow-up. The exclusion of other possible causes of leukoerythroblastosis such as invasion of the bone marrow with the leukemic clone or infections and the absence of acute hemolysjs or sepsis together with resolution of the condition after the discontinuation of treatment have defined G-CSF as the responsible factor for this unexpected finding. After 6 months of follow-up, the patient remains in remission, which can be taken as evidence that leuko- erythroblastosis associated with G-CSF administration is a transient and benign condition. We agree with Reykdal et al. [ I ] that the appearance of blasts may not always indicate relapse, such unexpected effects of G-CSF should always be kept in mind.

MUSTAFA ARICI

MUSTAFA.ERMAN OSMAN OZCEBE

iBRAHlM c. HAZNEDAROGLU

Deparfment of Hematology, Hacettepe University Medical School, Ankara, Turkey

REFERENCES

1. Reykdal S, Sham R, Phatak P, Koudies P: Pseudoleukemia following the use of G-CSF. Am J Hematol 49:258-259, 1995.

2. Lieschke GI, Burgess AW: Granulocyte colony-stimulating factor and granulocyte- macrophage colony-ytimulating factor. N Engl J Med 127:28-35, 99-106, 1992.

Possible Cytokine Mechanism of Increased Megakaryocytic Proliferation in 5q- Syndrome

To the Editor: We read with interest the excellent article about hematologic features of patients with chromosome Sq deletion by Lewis et al. in the July 1995 issue of the American Juurnul of Henzaiolugy [ I ] . The 5q- syndrome is a clonal hematologic disorder characterized by hypolobulated micromegakaryocytic hyperplasia and a clonal cytogenetic anomaly con- sisting of an interstitial deletion of the long arm of chromosome 5 (Sq-). Increased megakaryocytic proliferation with the characteristic megakaryo- cyte morphology and the concomitant presence of normal or high platelet counts and leukopenia are from specific features of the Sq- syndrome [ l f .

The proliferation and differentiation of hematopoietic cells is under the control of specific growth factors. Several major hematopoietic growth factors, including interleukin-4 (IL-4), acting on myeloid progenitors are located in the long arm of chromosome 5. On the other hand, the megakaryo-

marrow, increased hypolobular micromegakaryocytes, and increased ery- throid activity with 10-30% dyserythropoietic precursors. Cytogenetic anal- ysis revealed the Sq deletion breakpoints as (q13:q33). No additional karyo- typic abnormality has been found. Serum IL-6 and IL-4 concentrations were 68.3 pglml and 0 (undetectable) pg/ml, respectively, in this patient with 5q- syndrome associated with marked thrombocytosis and leukopenia. Normal median serum levels of IL-6 and 1L-4, which had been detected in 1.5 [8 women and 7 men; median age, 26 (range, 24-36)] healthy volun- teers with normal platelet counts (range, 191,000-38S,000/mm’), were 5.7 (range, 2 5 2 1 . 6 ) pg/ml and 33.6 (range, 5.1-107.2) pg/ml, respectively, in our enzyme-linked immunosorbent assay laboratory. Therefore, serum IL-6 level was notably increased in this patient with 5q- syndrome while the IL-4 level was found to be significantly decreased.

IL-4 may function directly as a negative regulator of megakaryocyto- poiesis and also it inhibits IL-6 synthesis and suppresses IL-6 production in vitro [5,6]. Increased IL-6 concentration in the patient might be due to decreased IL-4 synthesis by reason of the deletion of Sq. IL-6, which has achromosomal location of7p IS, is a well-known megakaryocyte potentiator [7-91. Consequently, leukopenia and thrombocytosis in the Sq- patient may be explained by decrease in cytokine interactions by the deletion of the long arm of chromosome 5. Nevertheless, further studies are needed to determine the association between clinical/laboratory hematologic fea- tures of patients with chromosome Sq deletion and hematopoietic cytokines.

YVCEL USTVNDAG

OSMAN OZCEBE SEMRA DUNDAR

SERAFETTIN KIRAZLI

iBRAHlM c. HAZNEDAROGLU

Deparfment of Hematology, Hacettepe University Medical School, Ankara, Turkey

REFERENCES

1. Lewis S, Oscier D, Boultwood J, Ross F, Fitchett, Rack K, Ahrahamson G, Buckle V, Wainscoat JS: Hematological features of patients with myelodysplastic syn- dromes associated with a chromosome 5q deletion. Am J Hematol 49:19&200, 1995.

2. Tcfferi A, Mathew P, Noel P The 5q- syndrome: A scientific and clinical update. Leuk Lymphoma 14:375-378, 1995.

3. Robinson BE, Quesenherry PJ: Hematopoietic growth factors: Overview and clini- cal applications. Parts I, 11 and 111. Am J Med Sci 300:163, 237, 31 I . 1990.

4. Hasnedaroglu IC, Ertenli I, Oscebe 01, Kiraz S, Ozdemir 0, Sayinalp NM, Dundar SV, Calgiineri M, Kirazli $: Megakaryocyte-related interleukins in reactive throm- hocytosis versus autonomous thromhocythemia. Acta Haematol (in press).

5. Sonoda J, Kuruyama Y, Tanaka S , Yokota S, Maekawa T, Clark SC, Ahe T Human interleukin 4 inhibits proliferation of megakaryocyte progenitor cells in culture. Blood 81:624-630, 1993.

6. Loyer P, llyin G. Razzak ZA, Banchereau J, Desier JF, Campion JP, Guguen- Guillouro C, Guillouzo A: Interleukin 4 inhibits the production of some acute- phase proteins by human hepatocytes in primary culture. FEBS Lett 336:215, 1993.

7 . Tefferi A, Ho T, Ahmann GJ, KatLmann JA, Greipp PR: Plasma interleukin-6 and C-reactive protein levels in rcactive versus clonal thrombocytosis. Am J Med 97314-378, 1994.

8. Sayinalp NM, Haznedaroglu lC, Ozdemir 0, Orcehe 01, Dundar SV, Kirazli 7: Interleukin-1 p and interleukin-6 in clonal versus reactive thrombocytosis. Eur J Haematol (in press).

9. Harnedaroglu IC, Sayinalp NM, Ozcehe 01, Ozdemir 0, Dundar SV, Kirazli $: Megakaryocytopoietic cytokines in autoimmune thrombocytopenic purpura. Am J Hematol 49:265, 1995.

cytopoietic cytokine IL-6, which seems to be responsible for megakaryocy- topoiesis in many cases of reactive thrombocytosis, is located in a different chromosomal location, 7pIS [3,4].

A 32-year-old male patient was admitted to our hospital with the com- plaints of low-grade fever, malaise, and weight loss. On admission, he had leukopenia (white blood cell count, 1,800/mm1, with 40% neutrophils in peripheral blood), macrocytic anemia (hemoglobin and mean corpuscular volume, 11.3 g/dl and 92 fl, respectively), and thrombocytosis (platelet count, 996,00O/mm’). Bone marrow examination showed a hypercellular

Iron Granules in Plasma Cells: Aspect

To the Editor: Iron granules in plasma cells were described in 1938 in a patient with hemochromatosis [ I ] . They are stained yellow-brown in May-

A Particular Morphologic

Letters and Correspondence 125

Fig. 1. A: Bone marrow smear stained by the May-Grunwald-Giemsa method. Arrow, iron granule. (High-magnification, XI ,000.) B: Bone marrow smear stained by Perk’ Prussian blue and counter- stained with safranin 0.1%. This stain verifies the hemosiderin nature of the granules. Arrow, iron granule. (High magnification, XI ,000.)

Grunwald-Giemsa bone marrow smears (Fig. lA), but they are blue in Perk’ Prussian blue stain with safranin 0.1% counterstain (Fig. IB).

In 1991 we reported our experience with two male patients, both with excessive drinking habits and macrocytic anemia without megaloblasts; one patient also had liver cirrhosis [2]. Now we report on the presence of iron granules in plasma cells, quantitated as grade 1 [3], in a 91-year-old female patient admitted for anorexia and asthenia. The patient had a previous significant history of breast cancer removed surgically (quadrantectomy). Laboratory tests showed a macrocytic anemia, with mild leucocytopenia. Bone marrow aspiration did not show megaloblastosis. Nodular biopsy on the breast scar showed the presence of neoplastic cells.

We refer to the morphologic aspect because only a few cases have been reported, although the technique employed for identification is easy to use. Both the source of the phenomenon and the causal mechanism are unknown.

It has not yet been determined whether the presence of iron granules in plasma cells could be the expression of a specific nosologic entity.

GUIDO D’ANGELO PAOLO CUERONI

Laboratorio di Chimica-Clinica, fmatologia e Microbiologia,

IVANO COSINI Unita di Medicina, Ospedale A.Bellini -21019, Somma Lombardo, Varese, Italy

REFERENCES

1 . Jabbe JB: The reticulo-endothelial system. In Downey NY (ed): “Handbook of

2. D’ Angelo G, Giardini C. Zanco MD: With regards to the presence of iron granules

3. McCurley TL, Cousar JB, Graher SE, Glick AD, Collins RD: Plasma cells iron

Hematology.” New York: 1938, p. 1170.

in plasma cells. Rec Prog Med 82675-676, 1991.

and morphologic features. Am J Clin Pathol 81:312-316, 1984.

Hornozygous Thalassernia and Difficult Endotracheal lntubation

To the Editor: Difficulty in airway management constitutes and essential predisposing factor of morbidity and mortality attributable to anesthesia, especially when it is not anticipated preoperatively [ I ] . With this in mind,

we investigated the epidemiological characteristics in difficult endotracheal intubation in regard to the presence of protruding maxilla in homozygous thalassemia patients.

Data were collected in a series of 5,166 anesthetic case records of consecutive adult patients undergoing general anesthesia for routine surgery. Fifteen specialist anesthetists carried out the routine preoperative airway assessment using standardised guidelines. Table I shows eight individual risk factors implicated to cause difficulty in intubation [ 1-31, Hypertrophy of the maxilla was defined as forward protrusion of the upper incisors beyond the lower incisors. Anesthesia was induced intravenously; 1 min after administration of succinylcholine 1 .5 mg.kg-’ tracheal intubation was carried out using a Macintosh laryngoscope, blade #3 or 4. Severity of difficulty in intubation was estimated according to the view obtained at laryngoscopy [4] (arytenoids and/or glottis = easy; only epiglottis or not even epiglottis = difficult).

Homozygous thalassemia patients had a notable prevalence in the series studied (58/5,166; 1.1%); however, it was not indicative of the general population [S], as our hospital is a referral center for the disease. It is widely accepted that hemoglobin levels are inversely correlated with maxilla size. According to our findings, the relative prevalence of patients with no evidence of hypertrophy of the maxilla was 26/58 (44.8%), reflecting the effectively followed-up homozygous thalassemia patients. Statistical analy- sis revealed a highly significantly increased risk of difficult intubation amongst patients presented with hypertrophy of maxilla due to thalassemia, as compared to patients with no evidence of any risk factor (Table I, probability of difficulty: 18.8% vs. 0.9%, two-tailed P-value = 0.0017, Fisher’s exact test; relative risk: 20.7, 9.5 < RR < 45.2, 95% Taylor series confidence limits).

In conclusion, homozygous thalassemia, when accompanied by maxillary deformity, constitutes an aggravating factor for difficult intubation. It proved to be of statistically equal strength when compared to traditionally recog- nised risk factors (Table I).

GREGORY S. VOYAGE KYRIAKOS P. KYRIAKIS

Department of Anesthesiology, Laikon General Hospital, Athens, Greece

REFERENCES

1. Benumof JL: Management of the difficult airway. Anesthesiology 75:1087, 1991. 2. Otto CW: Tracheal intubation. In Nunn JF, Utting JE, Brown BR (eds): “General

Anesthesia” Ed 5. London: Butterworths, 1989.